GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers

Abstract

Introduction: Growth hormone (GH) is an essential regulator of growth, body composition and fuel metabolism and, consequently, GH secretion is under the feedback control of numerous nutritional and endocrine mediators. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to exert pleiotropic effects, including stimulation of the activity of the hypothalamic-pituitary-adrenal axis. As GLP-1RAs exert multiple metabolic effects, we hypothesised that they may also affect the secretion of GH and examined the effect of a short-acting and a long-acting GLP-1 RA on GH secretion.

Methods: This is a post hoc analysis of data from clinical trials. Two separate single-group open-label clinical trials were carried out in the ambulatory care setting with a duration of 1 and 21 days, respectively. Healthy adult male and female volunteers with no chronic illnesses or use of daily medicines were recruited for the study. The two interventions were: study 1, single dose of 10 µg exenatide administered subcutaneously (s.c.); study 2, 0.6 mg liraglutide administered s.c. once daily for 21 days.

Results: Administration of a single dose of exenatide (study 1) caused a clear increase in GH levels, peaking between 60 and 120 min post-administration. There was also a small but statistically significant decrease in luteinising hormone and testosterone levels 120 min after exenatide dosing. Administration of the long-acting GLP-1RA liraglutide daily for 21 days (study 2) elicited an increase in GH levels with no change in insulin-like growth factor-1 (IGF-1) concentrations after 3 weeks of treatment.

Conclusions: The results show that the administration of GLP-1RAs may elicit an increase in growth hormone levels. GLP-1 signalling may be a novel mechanism of regulation of GH secretion. This finding needs to be replicated in the placebo-controlled trial.

Clinical trial registration numbers: NCT02089256 and NCT03160261.

Keywords: Exenatide; GLP-1 receptor agonist; Growth hormone.

Fig. 1

A Growth hormone (GH) pre-treatment and peak value after administration of 10 µg exenatide subcutaneously (s.c.) Asterisk indicates a significant difference at *p < 0.05 (Wilcoxon signed-rank test). B GH values at pre-specified sampling points depicted as timeline. Asterisk indicates a significant difference at *p < 0.05 (Dunn’s test). C GH levels at baseline and after acute and chronic treatment with 0.6 mg liraglutide s.c. Asterisks indicate a significant difference at *p < 0.05, **p < 0.01 (Dunn’s test). D Insulin-like growth factor 1 (IGF-1) levels at baseline, and after acute and chronic treatment with 0.6 mg liraglutide s.c. Asterisk indicates a significant difference at *p < 0.05 (Tukey test). GH data are depicted as the median with range; IGF-1 data are given as the mean with standard deviation (SD). Reference values: GH < 5 ng/mL; IGF-1 116–353 µg/L

Fig. 2

Correlation between GH peak values and change in glucose levels in the exenatide experiment (study 1). Pearson correlation, p = 0.207

Fig. 3

A Luteinising hormone (LH) levels at baseline and at 120 min after administration of 10 µg exenatide. B Testosterone levels at baseline and at 120 min after administration of 10 µg exenatide. Asterisk indicates a significant difference at *p < 0.05 (Tukey test). Data are depicted as the mean with SD. Reference values: LH 1.7–8.6 U/L; testosterone 6.68–29.0 nmol/L

Fig. 4

Change in prolactin (A) and copetine (B) levels. Asterisks indicate a significant difference at *p < 0.05 and **p < 0.01 (Tukey test). Data are depicted as mean with SD. Reference values: prolactin (males) 86–324 mU/L, (females) 102–496 mU/L; copeptine 1.0–28.2 pmol/L